Severe Class III Lupus Nephritis With Concurrent Thrombotic Microangiopathy and Suspected Atypical Hemolytic Uremic Syndrome Requiring Complement Blockade: A Complex Multisystem Presentation

Systemic lupus erythematosus (SLE) is frequently complicated by lupus nephritis (LN), but the coexistence of thrombotic microangiopathy (TMA) represents a rare and severe manifestation associated with poor renal outcomes. Differentiating between SLE-associated TMA and primary complement-mediated atypical hemolytic uremic syndrome is diagnostically challenging but critical, as it dictates the use of targeted therapies such as terminal complement inhibitors. A 36-year-old female with SLE, lost to follow-up for two years, presented with fatigue, seizures, and anuric renal failure. Laboratory studies revealed severe bicytopenia, metabolic acidosis, and hemolysis with normal ADAMTS13 activity. A renal biopsy confirmed International Society of Nephrology/Renal Pathology Society Class III LN with prominent superimposed TMA. Despite intensive management with high-dose steroids, plasma exchange, and hemodialysis, the patient’s refractory state necessitated the initiation of eculizumab. The clinical course was further complicated by a positive direct anti-globulin test (C3 positive/IgG negative), requiring intravenous immunoglobulin for a suspected secondary immune-mediated anemia. This case illustrates the diagnostic complexity of LN-TMA and the therapeutic necessity of a multidisciplinary approach. It underscores the importance of early renal biopsy and the timely utilization of complement inhibition in refractory cases to mitigate irreversible renal damage.